EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Combination benefit of a pyrimidylpiperazine derivative (Y-40138) and methotrexate in arthritic rats



Combination benefit of a pyrimidylpiperazine derivative (Y-40138) and methotrexate in arthritic rats



European Journal of Pharmacology 497(3): 351-359



Anti-tumor necrosis factor-alpha (TNFalpha) antibody in combination with methotrexate dramatically decreases joint destruction in rheumatoid arthritis. The aim of this study was to examine combined treatment with N-(1-(4- ((4-(pyrimidin-2-yl)piperazin-1-yl)methyl)phenyl)cyclopropyl) acetamide HCl (Y-40138) and methotrexate in rat adjuvant-induced arthritis. The increase in hindpaw volume and joint destruction was suppressed by single therapeutic administration (days 15-20) of Y-40138 (30 mg/kg, p.o.), but not by prophylactic administration (days 1-9). However, arthritic progression was suppressed by single prophylactic administration of methotrexate (0.3 mg/kg, p.o.), but not by therapeutic administration. Combined administration (days 10-20) of Y-40138 (0.3-1 mg/kg) and methotrexate (0.03 mg/kg) synergistically suppressed the increase in hindpaw volume and joint destruction. We concluded that Y-40138 in combination with methotrexate synergistically suppressed arthritic progression. These data suggest that combined treatment with Y-40138 and methotrexate may increase efficacy of therapy for rheumatoid arthritis. Copyright 2004 Elsevier B.V. All rights reserved.

(PDF emailed within 0-6 h: $19.90)

Accession: 011874205

Download citation: RISBibTeXText

PMID: 15336954

DOI: 10.1016/j.ejphar.2004.07.058



Related references

The biphasic immunoregulation of pyrimidylpiperazine (Y-40138) is IL-10 sensitive and requires NF-kappaB targeting in the alveolar epithelium. British Journal of Pharmacology 133(1): 49-60, 2001

Effects of interleukin-1 receptor antagonist alone and in combination with methotrexate in adjuvant arthritic rats. Arthritis & Rheumatism 40(9 SUPPL ): S181, Sept, 1997

A novel combination of methotrexate and epigallocatechin attenuates the overexpression of pro-inflammatory cartilage cytokines and modulates antioxidant status in adjuvant arthritic rats. Inflammation 35(4): 1435-1447, 2013

Effects of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) alone and in combination with methotrexate in adjuvant arthritic rats. Clinical and Experimental Rheumatology 17(5): 553-560, 1999

Combination benefit of PEGylated soluble tumor necrosis factor receptor type I (PEG sTNF-RI) and dexamethasone or indomethacin in adjuvant arthritic rats. Inflammation Research 48(8): 453-460, 1999

Methotrexate suppresses passive adjuvant arthritis: studies on the metabolism of methotrexate in mononuclear cells derived from normal and adjuvant arthritic rats. Journal of Rheumatology 15(8): 1193-1197, 1988

Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone. Arthritis and Rheumatism 56(12): 3919-3927, 2007

Pharmacokinetics, pharmacodynamics and toxicities of methotrexate in healthy and collagen-induced arthritic rats. Biopharmaceutics & Drug Disposition 34(4): 203-214, 2013

Low dose methotrexate treatment restored peripheral blood cell abnormalities of adjuvant arthritic rats. Federation Proceedings 45(3): 332, 1986

Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporin-A or methotrexate. International Journal of Immunopharmacology 10(6): 717-728, 1988

Prostaglandin and tumor necrosis factor secretion by peritoneal macrophages isolated from normal and arthritic rats treated with liposomal methotrexate. Journal of Pharmacological & Toxicological Methods 32(1): 53-58, 1994

Anti-oxidative and TNF-α suppressive activities of puerarin derivative (4AC) in RAW264.7 cells and collagen-induced arthritic rats. European Journal of Pharmacology 666(1-3): 242-250, 2011

Therapeutic index of methotrexate depends on circadian cycling of tumour necrosis factor-alpha in collagen-induced arthritic rats and mice. Journal of Pharmacy and Pharmacology 61(10): 1333-1338, 2010

A randomized prospective comparison of intermittent methotrexate methotrexate with leucovorin and a methotrexate combination in head and neck cancer. Cancer 48(5): 1061-1072, 1981